The present invention relates to serine carbonates and the use of serine carbonates as precursors for (a) organoleptic compounds, especially for fragrances, flavors and/or (b) masking agents, and/or (c) antimicrobial compounds and/or (d) alternative substrates for malodor producing enzymes.
A principal strategy currently employed in imparting odors to consumer products is the admixing of a fragrance, masking agent or antimicrobial compound directly into the product to be treated. There are, however, several drawbacks to this strategy. The fragrance material can, for example, be too volatile and/or too soluble, resulting in fragrance loss during manufacturing, storage and use. Many fragrance materials are also unstable over time. This again results in loss during storage.
In many consumer products it is desirable for the fragrance to be released slowly over time. Microencapsulation and inclusion complexes, especially with cyclodextrins, have been used to help decrease volatility, improve stability and provide slow-release properties. However, these methods are for a number of reasons often not successful. In addition, cyclodextrins can be too expensive.
In consumer products such as deodorants, the aim is to mask malodor or to block its production and optionally also to provide a pleasant fragrance. Deodorants are generally of three types: odor maskers, antiperspirants, and germicides. Despite the many disclosures in the art pertaining to deodorant compositions, current products are not sufficient to suppress odor in a significant proportion of the population, particularly during periods of stress. There remains a need for new deodorant compositions and methods which are effective, safe and economical.
Carbonate-derived fragrance precursors having mercapto or ether groups useful for laundry, deodorant and other applications are described in EP 816 322.
WO 91/11988 refers to alternative enzyme substrates as deodorants. The substrates are amino acids containing an 0-acyl or 0-thio group.
U.S. Pat. No. 5,431,904 relates to a deodorant composition comprising a compound which is capable of serving as an alternative substrate. Disclosed is a deodorant composition comprising O-acylated serine derivatives which compete with the naturally occurring malodor producing precursor. In a preferred embodiment, the O-acylated serine may generate organoleptic acids in the axilla concomitant with suppressing the malodor.
An object of the present invention is to provide new precursors for organoleptic and/or antimicrobial compounds and/or alternative substrates for malodor producing enzymes.
A further object of the invention is to provide such new precursors which are stable under usual transport and storage conditions. Optionally, the precursors of the present invention may release more than one active component.
It has now been found that serine carbonates of formula I 
or a salt thereof
wherein
R1 is the residue of an organoleptic alcohol, phenol or of the enol form of an organoleptic aldehyde or ketone of formula R1OH,
R2 is hydrogen, metal, ammonium, straight or branched alkyl, alkenyl, alkinyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl or heteroaryl, whereby all organic residues may contain heteroatoms and may carry substituents and if R2 is hydrogen R1 is not the residue of benzyl alcohol,
R3, R4 and R7 are independently hydrogen or lower alkyl and either R3 and R4 or R3 and R7 or R4 and R7 may form together a ring,
R5 and R6 are independently hydrogen, straight or branched alkyl, alkenyl, alkinyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, an aromatic or hetero aromatic residue, alkylcarbonyl, alkoxycarbonyl, arylcarbonyl, aryloxycarbonyl and R5 and R6 may together form a ring, whereby all organic residues may contain heteroatoms and may carry substituents, fulfill the aforementioned tasks and, hence, are useful for the aforementioned purposes.
The compounds of formula I are not limited to any particular stereoisomers, all possible stereoisomers (E/Z isomers, enantiomers, diastereomers) and all mixtures are thus included within the scope of the invention. Salts are also included in the general formula.
The compounds of formula I may be prepared as quaternary salts.
R2, R5 and/or R6 may contain heteroatoms selected of from the group O, N, S, P and Si.
R2, R5 and/or R6 may also carry one or more of the following substituents -halogen, -aryl, -heteroaryl, cycloalkyl, -cycloalkenyl, -heterocycloalkenyl, xe2x80x94OH, xe2x80x94OR, xe2x80x94NCOONxe2x95x90CR2, xe2x80x94OCOONxe2x95x90CR2, xe2x80x94COONxe2x95x90CR2 xe2x80x94NO2, xe2x80x94COR, xe2x80x94C(OR)2R, xe2x80x94COOR, xe2x80x94CONR2, OCOR, xe2x80x94OCOOR, OCONR2, xe2x80x94NR2, xe2x80x94SOR, xe2x80x94SO2R, xe2x80x94SO3R in which R is an organic residue.
R2 is preferably the residue of an organoleptic alcohol, phenol or of the enol form of an organoleptic aldehyde or ketone. However, compounds of formula I in which R2 is the residue of a non-organoleptic alcohol, phenol or of the enol form of a non-organoleptic aldehyde or ketone are also useful. R2 contains generally 1 to 30, preferably 1 to 20 C-atoms.
In particular R1 can be alkyl, alkenyl, cycloalkyl, cycloalkenyl, alkylcycloalkyl or aralkyl; R2 hydrogen, alkyl or aralkyl, R5 and/or R6 hydrogen, alkyloxycarbonyl, aryloxycarbonyl, arylalkoxycarbonyl or trialkylsilylalkoxycarbonyl.
Further preferred are compounds of formula I with R2 to R7 being hydrogen.
The compounds of formula I are mostly or nearly odorless at room temperature, atmospheric conditions and about 20 to 100% relative humidity. However, under activating conditions, they are cleaved and one or more active compounds, alcohols, phenols, aldehyes, and/or ketones, optionally with organoleptic and/or antimicrobial properties are generated.
The activating conditions which lead to cleavage of the precursors and thereby to the liberating of the desired active compound(s) may comprise the presence of skin bacteria, especially axilla bacteria, or of an enzyme such as protease or lipase, or elevated temperature or acidic or alkaline pH-values or a combination of two or more of these activating conditions.
In the specific case of usage as alternative substrates, the mechanism may be quite complex. Axillary malodor is generated by certain skin bacteria in the presence of apocrine secretion. Two strains of bacteria which produce axillary malodor when incubated with human apocrine secretions are Staphylococcus and several Coryneform isolates. Production of human axillary malodor can be assayed from these strains of bacteria by incubating cells with apocrine secretions collected from human axilla that has been sterilized in a phosphate buffer at pH 6.8.
The conversion of the naturally occurring apocrine secretion to axillary malodor occurs within the bacterial cells. Extracts of bacteria are capable of converting the apocrine secretion to the malodor compound in an enzymatic process. One of the malodor forming enzymes has been found to be a pyridoxal phosphate dependent amino acid lyase. The enzyme acts to cleave amino acids with the general structure HOOCxe2x80x94CH(NH2)xe2x80x94CH2xe2x80x94XR where X is S or O. The products of the reaction are pyruvate, ammonia, and RXH.
The naturally occurring precursor to axillary malodor in the apocrine secretion is a sulfur containing amino acid. The production of axillary malodor is blocked if an alternative substrate for the malodor forming enzyme is provided, so that the alternative substrate is cleaved instead of the apocrine precursor. The alternative substrates produce either a neutral odor or a pleasant odor upon cleavage.
The presence of alternative substrates (in the axilla) leads to competition with the natural precursor, which is present in low quantities, typically about one nanomole/axilla. Such competition almost completely prevents the malodor precursor from being converted. These compounds therefore serve as deodorants.
It has been surprisingly found that compounds of formula I are useful as alternative substrates competing with the naturally occuring malodor precursors.
Further the compounds of formula I, upon cleavage, provide at least one alcohol, phenol, aldehyde or ketone, all having organoleptic and/or antimicrobial activity and therefore permit the development of useful consumer products with enhanced organoleptic and/or antimicrobial properties. The organoleptic alcohols, phenols, aldehydes, and ketones obtained are useful as fragrances, masking agents and/or antimicrobial agents. Therefore, the invention also relates to the use of all compounds of formula I as precursors for organoleptic compounds, e.g., fragrances, flavors, masking agents, and/or as precursors for antimicrobial agents.
The serine carbonates of formula I can act as precursors in personal care products such as deodorants, in laundry products, cleaning compositions such as all-purpose and hard surface cleaners, pet care products and environment scents such as air fresheners. They can also act as precursors for an odor masking agent and at the same time in the same product as fragrance precursor. They also can act as precursors for antimicrobial agents for these and further products. In deodorants the compounds of formula I act as alternative substrates to the naturally occuring malodor producing enzymes and as precursors for organoleptic and/or antimicrobial substances. The fragrance precursors and the precursors for odor masking agents of the invention may be used individually in an amount effective to enhance or to mask the characteristic odor of a fragrance or a material. More commonly, however, the compounds are mixed with other fragrance components in an amount sufficient to provide the desired odor characteristics. Any person skilled in the art will have knowledge how to make best use of the precursors of the invention.
Due to the in situ generation of the active compounds the desired effect is prolonged and the substantivity of different substrates is enhanced. If two or more active compounds are provided, they can be generated, depending on the precursor and/or the activating conditions, simultaneously or successively. Further, the precursors of the invention provide slow release of the active compounds.
Examples of organoleptic alcohols and phenols include:
amyl alcohol
hexyl alcohol*
2-hexyl alcohol*
heptyl alcohol*
octyl alcohol*
nonyl alcohol*
decyl alcohol*
undecyl alcohol*
lauryl alcohol*
myristic alcohol
3-methyl-but-2-en-1-ol*
3-methyl-1-pentanol
cis-3-hexenol*
cis-4-hexenol*
3,5,5-trimethyl hexanol
3,4,5,6,6-pentamethylheptan-2-ol*
citronellol*
geraniol*
oct-1-en-3-ol
2,5,7-trimethyl-octan-3-ol
2-cis-3,7-dimethyl-2,6-octadien-1-ol
6-ethyl-3-methyl-5-octen-1-ol*
3,7-dimethyl-octa-3,6-di-1-enol*
3,7-dimethyloctanol*
7-methoxy-3,7-dimethyl-octan-2-ol*
cis-6-nonenol*
5-ethyl-2-nonanol
6,8-dimethyl-2-nonanol*
2,2,8-trimethyl-7-nonen-3-ol and 2,2,8-trimethyl-8-nonen-3-ol*
nona-2,6-dien-1-ol
4-methyl-3-decen-5-ol*
dec-9-en-1-ol
benzylalcohol
2-methyl undecanol
10-undecen-1-ol
1-phenyl-ethanol*
2-phenyl-ethanol*
2-methyl-3-phenyl-3-propenol
2-phenyl-propanol*
3-phenyl-propanol*
4-phenyl-2-butanol
2-methyl-5-phenyl-pentanol*
2-methyl-4-phenyl-pentanol*
3-methyl-5-phenyl-pentanol*
2-(2-methylphenyl)-ethanol*
4-(1-methylethyl)-benzenemethanol
4-(4-hydroxyphenyl)butan-2-one*
2-phenoxy-ethanol*
4-(1-methylethyl)-2-hydroxy-1-methyl benzene
2-methoxy-4-methyl phenol
4-methyl-phenol
anisic alcohol*
p-tolyl alcohol*
cinnamic alcohol*
vanillin*
ethyl vanillin*
eugenol*
isoeugenol*
thymol
anethol*
decahydro-2-naphthalenol
borneol*
cedrenol*
farnesol*
fenchyl alcohol*
menthol*
3,7,11-trimethyl-2,6,10-dodecatrien-1-ol
alpha-ionol*
tetrahydro-ionol*
2-(1,1-dimethylethyl)cyclohexanol*
3-(1,1-dimethylethyl)cyclohexanol*
4-(1,1-dimethylethyl)cyclohexanol*
4-isopropyl-cyclohexanol
6,6-dimethyl-bicyclo[3.3.1]hept-2-ene-2-ethanol
6,6-dimethyl-bicyclo[3.1.1]hept-2-ene-methanol*
p-menth-8-en-3-ol*
3,3,5-trimethyl-cyclohexanol
2,4,6-trimethyl-3-cyclohexenyl-methanol*
4-(1-methylethyl)cyclohexyl-methanol*
4-(1,1-dimethylethyl)cyclohexanol
2-(1,1-dimethylethyl)cyclohexanol
2,2,6-trimethyl-alpha-propyl-cyclohexane propanol*
5-(2,2,3-trimethyl-3-cyclopentenyl)-3-methylpentan-2-ol*
3-methyl-5-(2,2,3-trimethylcyclopent-3-en-1-yl)pent-4-en-2-ol*
2-ethyl-4-(2,2,3-trimethylcyclopent-3-en-1-yl)but-2-en-1-ol**
4-(5,5,6-trimethylbicyclo[2.2.1]hept-2-yl)-cyclohexanol*
2-(2-methylpropyl)-4-hydroxy-4-methyl-tetrahydropyran*
2-cyclohexyl-propanol*
2-(1,1-dimethylethyl)-4-methyl-cyclohexanol*
1-(2-tert-butyl-cyclohexyloxy)-2-butanol*
1-(4-isopropyl-cyclohexyl)-ethanol*
2,6-dimethyl-oct-7-en-2-ol**
2,6-dimethyl-heptan-2-ol**
3,7-dimethyl-octa-1,6-dien-3-ol**
whereby * indicates the preferred organoleptic alcohols and phenols and ** indicate the more preferred organoleptic alcohols and phenols. 
Examples of organoleptic aldehydes include:
2,6,10-trimethylundec-9-enal**
1,2,3,4,5,6,7,8-octahydro-8,8-dimethyl-2-napthalenecarboxaldehyde
2-[4-(1-methylethyl)phenyl]-ethanal
2,4-dimethyl-cyclohex-3-ene-1-carboxaldehyde*
4-carboxaldehyde-1,3,5-trimethyl-cyclohex-1-ene*
1-carboxaldehyde-2,4-dimethyl-cyclohex-3-ene*
1-carboxaldehyde-4-(4-hydroxy-4-methylpentyl)-cyclohex-3-ene*
3,5,5-trimethyl-hexanal
heptanal*
2,6-dimethyl-hept-5-enal**
decanal**
dec-9-enal
dec-4-enal
2-methyldecanal*
undec-10-enal**
undecanal*
dodecanal**
2-methyl-undecanal**
tridecanal
2-tridecenal
octanal**
nonanal*
3,5,5-trimethylhexanal
2-nonenal
undec-9-enal**
2-phenyl-propanal*
4-methyl-phenyl-acetaldehyde*
3,7-dimethyl-octanal*
dihydrofarnesal**
7-hydroxy-3,7-dimethyl-octanal*
2,6-dimethyl-oct-5-enal
2-(4-(1-methylethyl)phenyl)-ethanal*
3-(3-isopropylphenyl)-butanal**
2-(3,7-dimethyoct-6-en-oxy)-ethanal
1-carboxaldehyde-4-(4-methyl-3-penten-1-yl)-cyclohex-3-ene*
2,3,5,5,-tetramethyl-hexanal
longifolic aldehyde
2-methyl-4-(2,6,6-trimethylcyclohex-2-en-1-yl)-butanal*
2-methyl-3-(4-tert-butylphenyl)propanal**
4-(1,1-dimethylethyl)-benzenepropanal*
2-[4-(1-methylethyl)phenyl]-propanal
alpha-methyl-1,3-benzodioxole-5-propanal*
3,7-dimethyl-oct-6-enal*
2-methyl-3-(p-isopropylphenyl)-propionaldehyde**
4-(4-hydroxy-4-methylpentyl)-cyclohex-3-en-1-carboxaldehyde**
alpha-methyl-1,3-benzodioxole-5-propanal*
1-carboxaldehyde-4-(1,1-dimethylethyl)-cyclohexane
4-(octahydro-4,7-methano-5H-inden-5-ylidene)-butanal
[(3,7-dimethyl-6-octenyl)oxy]-acetaldehyde**
whereby * indicates the preferred organoleptic aldehydes and ** indicate the more preferred organoleptic aldehydes. 
Examples of organoleptic ketones include:
2-heptyl-cyclopentanone
2,2,6,10-tetrametyltricyclo[5.4.0.0(6,10)]-undecan-4-one
benzylacetone*
octan-2-one*
heptan-2-one*
undecan-2-one*
carvone*
1,2,3,5,6,7-hexahydro-1,1,2,3,3,-pentamethyl-4H-inden-4-one*
methyl heptenone*
2,5-dimethyl-oct-2-en-6-one**
2-(butan-2-yl)-cyclohexanone*
2-hexyl-cyclopent-2-en-1-one*
2-(1-methylethyl)-5-methyl-cyclohexanone*
2-(2-methylethyl)-5-methyl-cyclohexanone*
3-methyl-cyclopentadecanone
4-(1,1-dimethylpropyl)-cyclohexanone*
3-oxo-2-pentyl-cyclopentaneacetic acid methyl ester**
1-(1,2,3,4,5,6,7,8-octahydro-2,3,8,8-tetramethyl-2-naphthalenyl)-ethanone*
3-methyl-5-propyl-cyclohex-2-en-1-one*
1-(4-hydroxyphenyl)-butan-3-one
whereby * indicates the preferred ketones and ** indicate the more preferred ketone. 
Compounds of formula I upon cleavage may also generate antimicrobial compounds. Examples of these compounds are e.g. presented by J. J. Kabara, Cosmet. Sci. Technol. Ser. (16) 1997, p 181-208, especially in Table 8.6.
Of course, the afore mentioned alcohols, phenols, aldehydes, ketones and antimicrobial compounds can serve mutually as fragrances, masking agents and/or antimicrobial compounds. A person of skill in the art is well aware of these interrelationships and can make use thereof to solve a specific problem by using the precursors of the present invention.
It is a matter of course, that it is not possible to give a complete list of the organoleptic and/or antimicrobial alcohols, phenols, aldehydes and ketones which are generated as a result of the desired cleavage of the compounds of formula I by skin bacteria, by enzymes, by elevated temperatures or by acidic and/or alkaline pH-values. The skilled person is, however, quite aware of those alcohols, phenols, aldehydes and ketones which provide the desired organoleptic properties, e.g. for being used as fragrance or for odor masking, and/or showing antimicrobial effects.
The compounds of formula I may preferably be used as sustained release odorants but also to mask or attenuate undesirable odors or to provide additional odors not initially present in consumer products, i.e. personal care products such as cosmetic products, underarm deodorants or antiperspirants or other deodorants contacting the body, or in hand lotions, hair care products such as shampoos and conditioners, baby powders, baby lotions, ointments, foot products, facial cleansers, body wipes, facial makeup, colognes, after-shave lotions, shaving creams, etc. Additional applications include laundry detergents, fabric softeners, fabric softener sheets, (automatic) dishwasher detergents and all-purpose and hard surface cleaners. Further applications are air fresheners and odorants, odor masking agents and/or antimicrobial agents.
The amount required to produce the desired, overall effect varies depending upon the particular compounds of formula I chosen, the product in which it will be used, and the particular effect desired.
For example, depending upon the selection and concentration of the compound chosen, when a compound of the formula I is added either singly or as a mixture, e.g. to a deodorant or laundry product composition at levels ranging from about 0.1 to about 10% by weight, or most preferred about 0.25 to about 4% by weight, an odorant, i.e. one or more odoriferous compounds in an xe2x80x9corganoleptically effective amountxe2x80x9d is released when the product is used. This newly formed odorant serves to enhance the odor of the product itself or of a fragrance present in the product.
Although deodorancy is the most important concern for the consumer of underarm products, many also choose a product with antiperspirant activity. Current antiperspirant compounds, which are aluminum salts, also function as deodorants by virtue of their germicidal properties.
Thus, if desired, the deodorants of the present invention can be employed with the antiperspirant salts well known in the art. In such formulations, the serine carbonates can be incorporated into a deodorant or antiperspirant formulation along with an antiperspirant salt wherein the antiperspirant salt may be employed in a perspiration reducing effective concentration, e.g., 6 to 30% or in a deodorant effective concentration, e.g., 1 to 6%.
The antiperspirant salt used in the present invention may be any of those which contain aluminum, either alone or in combination with other materials such as zirconium. Typical aluminum salts, although not all-inclusive, include:
aluminum chlorohydrate;
aluminum sesquichlorohydrate;
aluminum dichlorohydrate;
aluminum chlorohydrex PG or PEG;
aluminum sesquichlorohydrex PG or PEG;
aluminum dichlorohydrex PG or PEG;
aluminum zirconium trichlorohydrate;
aluminum zirconium tetrachlorohydrate;
aluminum zirconium tetrachlorohydrex PG or PEG;
aluminum zirconium pentachlorohydrate;
aluminum zirconium octachlorohydrate;
aluminum zirconium trichlorohydrex-gly;
aluminum zirconium tetrachlorohydrex-gly;
aluminum zirconium pentachlorohydrex-gly;
aluminum zirconium octachlorohydrex-gly;
aluminum zirconium chloride;
aluminum zirconium sulfate;
potassium aluminum sulfate;
sodium aluminum chlorohydroxylacetate;
aluminum bromohydrate.
In general, the active antiperspirant salt is present in the same amounts at which such materials are employed in prior art compositions. As a general rule, such compositions contain from about 3% to about 30% preferably from about 10% to about 25%, of the active antiperspirant salt component.
As is evident from the above compilation of alcohols, phenols, aldehydes and ketones, a broad range of known odorants can be generated from precursors of the invention. While manufacturing compositions the precursors of the invention may be used according to methods known to the perfumer, such as e.g. from W. A. Poucher, Perfumes, Cosmetics, Soaps, 2, 7th Edition, Chapman and Hall, London 1974.
Compounds of the formula I can be synthesized in a variety of ways known to those skilled in the art. Convenient methods are outlined in the Examples without limiting the invention thereto.
Compounds of formula I can be prepared by using a wide variety of methods known to the skilled chemist.
For example, for the synthesis of esters see Comprehensive Organic Chemistry, vol. 2, D. Barton, W. D. Ollis, Pergamon Press, p. 871-909
For example, for the synthesis of carbamates see Comprehensive Organic Chemistry, vol. 2, D. Barton, W. D. Ollis, Pergamon Press, p. 1083-1084
For example, for the synthesis of chloroformates see Comprehensive Organic Chemistry, vol. 2, D. Barton, W. D. Ollis, Pergamon Press, p. 1074-1078
For example, for the synthesis of carbonates see Comprehensive Organic Chemistry, vol. 2, D. Barton, W. D. Ollis, Pergamon Press, p. 1070-1072
For example, for the conversion of carbamates to amines and esters to acids see Protective Groups in Organic Synthesis, 2. edition, T. W. Greene, Peter G. M. Wuts, John Wiley and Sons, Inc., 1991